title: Revisiting clinical trials using EGFR inhibitor-based regimens in patients with advanced non-small cell lung cancer: a retrospective analysis of an MD Anderson Cancer Center phase I population.
abstract: OBJECTIVE
  Single-agent EGFR inhibitor therapy is effective mainly in patients with lung cancer and EGFR mutations. Treating patients who develop resistance, or who are insensitive from the outset, often because of resistant mutations, other aberrations or the lack of an EGFR mutation, probably requires rational combinations. We therefore investigated the outcome of EGFR inhibitor-based combination regimens in patients with heavily-pretreated non-small cell lung cancer (NSCLC) referred to a Phase I Clinic.
  
  
  METHODS
  We reviewed the electronic records of patients with NSCLC treated with an EGFR inhibitor-based combination regimen: erlotinib and cetuximab; erlotinib, cetuximab and bevacizumab; erlotinib and dasatinib; erlotinib and bortezomib; or cetuximab and sirolimus.
  
  
  RESULTS
  EGFR mutations were detected in 16% of patients (21/131). EGFR inhibitor-based combination regimens were administered to 15 patients with EGFR-mutant NSCLC and 24 with EGFR wild-type disease. Stable disease (SD) ≥6 months/partial remission (PR) was attained in 20% of EGFR-mutant patients (3/15; two with sensitive mutations and secondary resistance to prior erlotinib, and one with a resistant mutation), as well as 26% of evaluable patients (5/19) with wild-type disease. One of three evaluable patients with squamous cell histology achieved SD for 26.5 months (EGFR wild-type, TP53-mutant, regimen=erlotinib, cetuximab and bevacizumab).
  
  
  CONCLUSIONS
  Eight of 34 evaluable patients (24%) with advanced, refractory NSCLC evaluable for response achieved SD ≥6 months/PR (PR=3; SD ≥6 months=5) on EGFR inhibitor-based combination regimens (erlotinib, cetuximab; erlotinib, cetuximab and bevacizumab; and, erlotinib, bortezomib), including patients with secondary resistance to single-agent EGFR inhibitors, resistant mutations, wild-type disease, and, squamous histology.
authors.affiliation: Department of Investigational Cancer Therapeutics-Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Texas, USA. jjwheler@mdanderson.com
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wheler
authors.forename: Gerald
authors.initials: G
authors.lastname: Falchook
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Sarina
authors.initials: S
authors.lastname: Piha-Paul
authors.forename: Su S
authors.initials: SS
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Heymach
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Bettzy
authors.initials: B
authors.lastname: Stephen
authors.forename: Jansina Y
authors.initials: JY
authors.lastname: Fok
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D000068818:Cetuximab; D000069439:Dasatinib; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use; D013534:Survival; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001897:Boronic Acids; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D011743:Pyrimidines; D011799:Quinazolines; D013844:Thiazoles; D000068258:Bevacizumab; D000069286:Bortezomib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab; D000069439:Dasatinib; D020123:Sirolimus